In Vitro Activity of Imipenem-Funobactam and Relevant Comparators Against Acinetobacter baumannii-calcoaceticus Species Complex Isolates (2019–2020)

Background/Objectives: Antibacterial resistance in Gram-negative bacteria including carbapenem-resistant Acinetobacter baumannii-calcoaceticus species complex (A. baumannii SC) remains an urgent public health threat. Funobactam (formerly XNW-4107) is a novel diazabicyclooctane class β-lactamase inhibitor with potent activity against Class A, C, and D β-lactamases. Funobactam is in development with imipenem/cilastatin for the treatment of carbapenem-resistant Gram-negative pathogens and recently completed a Phase III clinical trial for hospitalized adults with nosocomial pneumonia (NCT05204563). This study evaluated the in vitro activity of imipenem-funobactam (fixed 8 µg/mL) and comparators against A. baumannii SC clinical isolates (n = 302), including carbapenem-resistant strains (n = 138), collected from medical centers worldwide in the SENTRY Antimicrobial Surveillance Program (2019–2020). Methods: Broth microdilution susceptibility testing of imipenem–funobactam and comparators followed Clinical and Laboratory Standards Institute M07 and M100 guidelines. Results: The combination of imipenem–funobactam restored imipenem activity from 53.0% susceptible to 91.1% susceptible against 302 A. baumannii SC isolates when applying the imipenem susceptibility breakpoint of ≤2 µg/mL to the imipenem–funobactam combination for comparison purposes only. Cefiderocol and colistin were the only comparator agents tested with susceptibility >90.0% against A. baumannii SC. Imipenem–funobactam (MIC50/90, 1/8 µg/mL) demonstrated good activity against a subset of carbapenem-resistant A. baumannii SC isolates, inhibiting 80.4% of all isolates at the imipenem-susceptibility breakpoint of ≤2 µg/mL. Conclusions: Despite the recent approval of sulbactam–durlobactam, treatment options for carbapenem-resistant A. baumannii (CRAB) remain limited. The potent in vitro activity and favorable pharmacokinetic profile of imipenem/cilastatin/funobactam support further investigation and development for serious infections caused by A. baumannii SC isolates including CRAB.